UCLA HEART FAILURE CLINICAL PRACTICE GUIDELINE SUMMARY-2005

UCLA HEART FAILURE CLINICAL PRACTICE GUIDELINE SUMMARY-2005 Medical Center Ahmanson-UCLA Cardiomyopathy Center Los Angeles, California Gregg C. Fonarow, MD, Director Ahmanson-UCLA Cardiomyopathy Center 1996, 1998, 2002, 2004, 2005 Regents of the University of California (Clinical Guideline Committee, UCLA Division of Cardiology) Permission to reprint may be granted by contacting Gregg C. Fonarow, MD UCLA Division of Cardiology, 47-123 CHS, 10833 LeConte Ave, LA, CA, 90095; Phone (310) 206-9112; Fax (310) 206-9111; e-mail gfonarow@mednet.ucla.edu CRG-922

Controlling Heart Failure and Improving Clinical Outcome Heart failure affects more than 5 million Americans, with more than 500,000 new cases occurring annually and a resultant 1,000,000 hospitalizations, which translates into an annual estimated cost of nearly $25 billion dollars. Mortality with this condition is high, approximately 50% at 5 years. Implementation of the advances in management of heart failure have the potential to improve patients' quality of life, reduce the need for hospitalizations, reduce total medical costs, and prolong survival. The approach to diagnosis and management of heart failure (HF) and the goals of therapy are outlined below. I. Definition Heart failure (HF) is a complex clinical syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the ventricle to fill with or eject blood. The cardinal manifestations of HF are dyspnea and fatigue, which may limit exercise tolerance, and fluid retention, which may lead to pulmonary congestion and peripheral edema. II. Etiology Common Less Common Coronary Artery Disease Hypertensive Heart Disease Idiopathic Dilated Cardiomyopathy Valvular Heart Disease Drugs - Alcohol, Cocaine, Methamphetamine Heart Failure with Preserved Systolic Function (Diastolic Dysfunction) Congenital Heart Disease Infiltrative Cardiomyopathy - Amyloid, Sarcoid, Restrictive Hemochromatosis Thyroid Disease Pheochromocytoma Chronic Kidney Disease HIV and Viral Cardiomyopathy 1

2 III. History and Physical Evaluation Evaluate for symptoms/signs of volume excess and/or low cardiac output Volume Excess Low Cardiac Output History Decreased Exercise Tolerance Decreased Exercise Tolerance SOB, DOE Fatigue PND Malaise Edema Decreased Appetite Weight Gain Weight Loss RUQ tenderness PE Rales (not always present) Cachexia Increased JVP Muscle Loss Hepatojugular Reflex/tenderness Cool Extremities Edema Tachycardia S3 S3 Narrow Pulse Pressure IV. Evaluation of HF All patients with HF should have initial assessment of left ventricular ejection fraction (echocardiogram). LVEF must be documented in medical record. Laboratory Electrolytes, BUN, Creatinine assess renal function CBC assess for anemia T4, TSH - exclude thyroid disease Liver Function Tests - evaluate for right heart failure Cholesterol panel (LDL) - evaluate risk for CAD, risk, and need for statin Urinalysis - exclude nephrotic syndrome Diagnostic Tests ECG prior infarct, LVH, arrhythmias CXR BNP (level <100 pg/ml, makes HF diagnosis unlikely) (also provides important information regarding prognosis) Cardiac troponin: evaluate for ACS and/or ongoing myocardial cellular injury Echocardiography - all patients should have assessment of LV function: quantitate LV size, evaluate hemodynamics, diastolic function, valvular heart disease, CAD, amyloid Additional Tests If at risk/suspected CAD (angina/mi/risk factors - ETT, Nuclear Imaging, PET scan or coronary angiogram) CPX (Cardiopulmonary exercise test). Quantitate functional capacity, access prognosis, guide exercise prescription Hospitalize for initial management or during follow-up for: Hypoxia - O2 <90% Pulmonary edema/anasarca/pneumonia Symptomatic hypotension (SBP <80 mm Hg) with significant volume overload Inadequate social support in the setting of decompensation of HF refractory to outpatient Rx Increasing renal dysfunction not due to overdiuresis; hepatic dysfunction Suspicion of low cardiac output status with low SBP (cardiac cachexia) V. Medication for HF - Systolic Dysfunction Neurohumoral antagonism is the cornerstone of heart failure management. Because of their beneficial effects on disease progression, functional status, hospitalizations, and mortality risk, ACE inhibitors, beta blockers, and aldosterone antagonists should be prescribed for all patients with left ventricular systolic dysfunction, unless specific, well-defined contraindications exist. Antagonism of Neurohumoral Activation ACE Inhibitors: Improve survival (17-37% mortality reduction) in patients with Class I-IV heart failure, asymptomatic LV dysfunction, myocardial infarction, hypertension, coronary artery disease, and diabetes. Additional benefits include reduced hospitalization, myocardial infarction, strokes, renal failure, and new-onset diabetes. Doses of ACE inhibitors should be titrated upward over time with the goal of reaching the target doses used in the prospective randomized clinical trials to reduce mortality. Monitor serum K+, BUN, Cr at least one week after initiation or dose change and periodically thereafter, earlier if significant renal dysfunction. HF patients with severe renal insufficiency and those on dialysis should be treated with ACE inhibitors. Contraindications: cardiogenic shock, angioneurotic edema, hyperkalemia, and pregnancy. Renal insufficiency is a double indication, not a contraindication. 3

4 Use Target (Survival) Doses Initiation Target Maximum Enalapril 5 mg bid 10 mg bid 20 mg bid Lisinopril 10 mg daily 20 mg daily 40 mg daily Captopril 25 mg tid 50 mg tid 100 mg qid Quinapril 10 mg bid 20 mg bid 40 mg bid Benazepril 10 mg daily 40 mg daily 80 mg daily Ramipril 5 mg daily 10 mg daily 20 mg daily Beta Blockers: Improve survival (34-65% mortality reduction) in patients with Class I-IV heart failure, asymptomatic LV dysfunction, myocardial infarction, hypertension, coronary artery disease, and diabetes. Additional benefits include reduced hospitalization, MI, and sudden death. Beta blockers should be initiated in all compensated heart failure patients, without contraindications. Patients requiring intravenous inotropic agents should have beta blocker therapy deferred until stabilized. Contraindications: cardiogenic shock, symptomatic bradycardia, 2nd- or 3rd-degree heart block without pacemaker, reactive airway disease. Note that diabetes, peripheral vascular disease, asymptomatic bradycardia, and COPD are not contraindications. Monitor patients for symptomatic hypotension or symptomatic bradycardia. Start at low dose with careful titration. Increase at intervals of at least 2 weeks until target dose. The ACC/AHA guidelines recommend using only those beta blockers and those doses that have been proven to reduce mortality (ie, mortality reduction is not a class effect). COMET demonstrated that carvedilol (beta-1, beta-2, and alpha-1 blockade) provided a 17% mortality reduction compared to beta-1 selective blockade with metoprolol tartrate. Initiation Titration Target Carvedilol (preferred) 3.125 mg bid 6.25, 12.5 25 mg bid mg bid Metoprolol XL 12.5 mg daily 25, 50, 100, 200 mg daily 150 mg daily Bisoprolol 1.25 mg daily 2.5, 5 mg daily 10 mg daily The COPERNICUS trial demonstrates survival benefits with carvedilol in patients with Class IV heart failure and that therapy can be initiated during hospitalization. IMPACT-HF demonstrates that inhospital initiation is safe and improves treatment rates. Strongly consider initiation of carvedilol or switching from other beta blockers to carvedilol prior to heart failure hospital discharge, as this has been shown to improve patient compliance and treatment utilization. For patients who are tenuous or who have failed a prior attempt at beta blocker initiation, ultra-low doses may facilitate initiation. One suggested regimen is to initiate carvedilol 3.125, 1/2 tab PO qhs (ie, 1.5625 mg). After one week, the dose is given bid, after 3 more weeks, the patient is advanced to 3.125 mg bid, then slowly titrated up from that level at 4 8-week intervals. Aldosterone Antagonism: Improve survival (15-30% mortality reduction) in patients with Class III-IV heart failure as well as patients with mild HF. Reduction in hospitalizations and sudden death also demonstrated. Indicated in all patients with systolic HF. Consider in HF with preserved systolic function. Aldosterone antagonists are administered in conjunction with ACE inhibitors, beta blockers, and frequently, loop diuretics. Since these agents are potassium-sparing diuretics, patients will likely require adjustment of potassium supplements, possible alteration in other diuretic dosing, and close monitoring of renal function and serum potassium levels. It is recommended that the dose of potassium supplements be reduced on initiation, check K+, BUN, Cr at 1 week and 4 weeks. After adjustments at 4 weeks, increase dose to target level, rechecking labs at 1 week and 4 weeks. Use extreme caution if serum Cr >2.5 mg/dl in men or Cr >2.0 mg/dl in women. Initiation Target Maximum Spironolactone 6.25 or 25 mg daily 25 mg daily 12.5 mg daily Eplerenone 12.5 or 50 mg daily 50 mg daily 25 mg daily Angiotensin Receptor Antagonists: Hemodynamic and symptomatic benefits demonstrated. ELITE II showed a low dose of the ARB losartan was not superior or equivalent to ACE inhibitor treatment. CHARM demonstrated benefits of ARB in ACE-intolerant patients as well as in patients on ACE inhibitors. Recommend use in patients that cannot tolerate or have unacceptable side effects with ACE inhibitors or as add-on therapy to ACE inhibitor, beta blocker, and aldosterone 5 antagonist, but not as first-line therapy instead of ACE inhibitor.

6 Initiation Target Maximum Losartan 25 mg bid 50 mg bid 100 mg bid Valsartan 40 mg bid 80-160 160 mg bid mg bid Candesartan 8 mg daily 32 mg daily 32 mg daily Hydralazine/Nitrates The combination of hydralazine with isosorbide dinitrate reduced mortality by 43% in African Americans with Class III HF when added to standard care. These agents work as nitric oxide (NO) donors. The therapeutic role of these agents in HF patients other than African Americans should be further evaluated, but this represents a reasonable option for all HF patients who remain Class III or IV, irrespective of race or ethnicity. Hydralazine 37.5-75 mg tid Isosorbide dinitrate 20-40 mg tid Symptomatic Treatments Digoxin No benefit, no harm on CHF mortality, decreases need for CHF hospitalizations, but not overall hospitalization. Use for afib rate control only (keep levels <1.0 ng/ml) Diuretics Loop diuretics with potassium supplementation Flexible regimen with doubled dose for 2-lb weight gain and prn metolazone Co-morbidities and Related Risks The majority of heart failure patients (60-70%) have coronary artery disease, other atherosclerotic vascular disease, and/or diabetes. They should receive comprehensive atherosclerosis treatment which includes aspirin, beta blocker, ACE inhibitor, and statin titrated to an LDL <70 mg/dl in conjunction with diet, omega-3 fatty acid supplementation, and exercise counseling. Statins may also provide benefit to heart failure patients regardless of etiology and cholesterol levels. Control of hypertension is also believed to be important, but optimal targets for SBP or DBP have not been established in HF patients. For patients remaining hypertensive despite ACE inhibitors, beta blockers, and aldosterone antagonists, recommend hydralazine/nitrates or, alternately, amlodipine or doxazocin. Gold standard, evidence-based, guideline-recommended therapy to decrease symptoms, reduce hospitalizations, and improve survival in HF is now treatment with ACE inhibitors, beta blockers, and aldosterone antagonists. Hydralazine/nitrate combination therapy has been demonstrated to reduce mortality. VI. Medication for HF with Preserved Systolic Function Although there are not randomized clinical trials available to guide therapy for patients with heart failure and preserved systolic function, these patients have similar etiologies, neurohumoral activation, functional impairment, and hemodynamics as patients with systolic dysfunction heart failure. Observational studies have suggested that ACE inhibitor and beta blocker use is associated with reduced morbidity and mortality in patients with heart failure and preserved systolic function. In addition, these patients frequently have comorbid conditions such as hypertension, coronary artery disease, and/or diabetes, where ACE inhibitors and beta blockers are of proven benefit. It is recommended based on pathophysiology, observational data, and expert opinion that patients with heart failure and preserved systolic function be treated with the same medical regimen recommended for heart failure with systolic dysfunction (ie, ACE inhibitor, beta blocker, aldosterone antagonist). VII. Device Therapy for HF LVEF 0.30, post MI: prophylactic ICD therapy indicated, reduces mortality by 31% (MADIT II). Wait >30 days after acute myocardial infarction before implanting ICD (DINAMIT) LVEF 0.35, Class II/III, all HF etiologies, ICD therapy reduces mortality by 23% (SCD-HeFT) QRS 120 ms, LVEF 0.35, NYHA Class III or IV: Cardiac resynchronization therapy plus ICD indicated, reduces mortality by 43% and death and hospitalization by 22% (COMPANION) Prophylactic placement of an ICD device (with or without CRT) is recommended in conjunction with optimal medical treatment in all eligible HF patients without contraindications, as part of standard management. Education and counseling of patients prior to device placement is essential. 7

VIII. Specific Clinical Scenarios Volume Excess ACE Inhibitor Beta Blocker Aldosterone Antagonist Loop Diuretic Low Output ACE Inhibitor Digoxin Aldosterone Antagonist Hydralazine/Isordil CAD/CVD/PVD ASA Statin ACE Inhibitor Beta Blocker Tachyarrhythmias Atrial fibrillation - Amiodarone Asymptomatic PVC - Beta Blockers NSVT and CAD - EPS, if induce, ICD Syncope, VT, or Sudden Death ICD Bradyarrhythmias D/C Digoxin Pacemaker - in NSR consider CRT in Afib consider CRT Indications for anticoagulation: atrial fibrillation, left ventricular thrombus, or prior systemic embolization. INR 2.0-3.0 IX. Medications to Avoid: Type I Antiarrhythmic Agents Increase risk of sudden death and mortality 3-4X Calcium Channel Blockers Increase risk of CHF admit, progressive ventricular dilation, and mortality NSAIDs and COX-2 Inhibitors Increase risk of renal dysfunction/failure X. Comprehensive Management Nonpharmacologic Therapies: Essential Components of Therapy Diet: 2 gram sodium diet with detailed education of patient and family members Fluid Restriction: 2 liter (64 oz) daily fluid restriction Daily Weights: Monitor and record daily weights, bring chart to each visit Flexible Diuretics: Patient-centered diuretic dosing, double for 2-lb wt gain, prn metolazone Daily Aerobic Exercise: Progressive walking program Patient Education: Detailed patient and family member education with frequent reinforcement Comprehensive Management combining optimization of heart failure medications and patient education can prevent up to 85% of heart failure hospitalizations and reduce total medical costs substantially XI. Management of Refractory Patients - Tailored Therapy Patients with severe decompensated HF and those that have failed empiric therapy may potentially benefit from cardiology referral and invasive monitoring. Potential indications for hemodynamic monitoring include: Increasing renal or hepatic dysfunction not due to overdiuresis Hypotension (SBP <80 mm Hg) with volume excess (increased JVP) Suspicion of low cardiac output status with low SBP (cardiac cachexia) Failing to respond to clinically guided dosing of ACE inhibitor, beta blocker, and diuretic therapy Decompensated patients are admitted and right heart catheter is placed. Intravenous nesiritide or nitroprusside and diuretics are titrated. Once optimal hemodynamics are achieved, ACE inhibition is started and the dose advanced while weaning the IV vasodilator. Patients who remain symptomatic despite aggressive medical therapy should be referred to a heart transplantation center for evaluation for orthotopic heart transplantation. Patients with advanced heart failure undergoing orthotopic heart transplantation currently have an expected 85-90% 1-year and a 70-75% 5-year survival. Selective patients age 65-70 (with additional risk factors) and those patients age 70-74 can be considered for UCLA s alternative heart transplantation program. 8 9

10 Implantable LV ventricular assist devices (TCI HeartMate and others) are available to mechanically bridge patients to cardiac transplantation. Studies to evaluate mechanical LV assist devices as long-term HF treatment without transplantation have been completed and show some benefit. Other experimental therapies such as myocyte transfer and stem cell transplantation are also undergoing further evaluation. XII. Prevention of Heart Failure Primary Prevention Stage A (prevent development of left ventricular dysfunction) Treat Hypertension, especially systolic hypertension (ACE inhibitor, beta blocker) Treat Hypercholesterolemia (statin, aspirin) Treat Atherosclerosis (aspirin, beta blocker, ACE inhibitor, statin) Treat Diabetes (aspirin, beta blocker, ACE inhibitor, statin, glycemic control) Weight loss for obese individuals Smoking cessation Secondary Prevention Stage B (prevent progression from asymptomatic LV dysfunction) ACE Inhibitor Beta Blocker Aldosterone Antagonist Secondary Prevention after Myocardial Infarction (Aspirin, Beta Blocker, ACE Inhibitor, Aldosterone Antagonist if LVD, Statin, Exercise) ICD (selected indications) Tertiary Prevention Stage C/D (prevent progression of clinical HF to mortality) ACE Inhibitor Beta Blocker Aldosterone Antagonist Hydralazine/Nitrate (selected indications) Secondary Prevention of Coronary Artery Disease ICD and/or Cardiac Resynchronization (selected indications) Exercise References 1. Stevenson LW, Fonarow G. Vasodilators. A re-evaluation of their role in heart failure. Drugs. 1992;43:15-36. 2. Armstrong PW, Moe GW. Medical advances in the treatment of congestive heart failure. Circulation. 1993;88:2941-2952. 3. Cohn JN, Johnson G, Ziesche S, et al. A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure. N Engl J Med. 1991;325:303-310. 4. Fonarow GC, Chelimsky-Fallick C, Stevenson LW, et al. Effect of direct vasodilation with hydralazine versus angiotensin-converting enzyme inhibition with captopril on mortality in advanced heart failure: the Hy-C trial. J Am Coll Cardiol. 1992;19:842-850. 5. Konstam M, Dracup K, Baker D, et al. Heart Failure: Evaluation and Care of Patients With Left-Ventricular Systolic Dysfunction. Clinical Practice Guideline No. 11. AHCPR Publication No. 94-0612. Rockville, MD: Agency for Health Care Policy and Research, Public Health Service, U.S. Department of Health and Human Services. June 1994. 6. Stevenson WG, Stevenson LW, Middlekauff HR, et al. Improving survival for patients with advanced heart failure: a study of 737 consecutive patients. J Am Coll Cardiol. 1995;26:1417-1423. 7. Packer M, Bristow MR, Cohn JN, et al. The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. U.S. Carvedilol Heart Failure Study Group. N Engl J Med. 1996;334:1349-1355. 8. The effect of digoxin on mortality and morbidity in patients with heart failure. The Digitalis Investigation Group. N Engl J Med. 1997;336:525-533. 9. Sackner-Bernstein JD, Mancini DM. Rationale for treatment of patients with chronic heart failure with adrenergic blockade. JAMA. 1995;274:1462-1467. 10. Pitt B, Segal R, Martinez FA, et al. Randomised trial of losartan versus captopril in patients over 65 with heart failure (Evaluation of Losartan in the Elderly Study, ELITE). Lancet. 1997;349:747-752. 11

11. Fonarow GC, Stevenson LW, Walden JA, et al. Impact of a comprehensive management program on hospitalization, functional status, and medical cost of patients with advanced heart failure. J Am Coll Cardiol. 1997;30:725-732. 12. Fonarow GC. Heart failure: recent advances in prevention and treatment. Rev Cardiovasc Med. 2000;1:25-33. 13. Hunt SA, Baker DW, Chin MH, et al. ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2001;104:2996-3007. 14. UCLA Cardiology Clinical Guidelines. www.med.ucla.edu/champ. 12